Malaria Immunity Trigger Found For Multiple Mosquito Species

March 16, 2009 — Researchers at the Johns
Hopkins Bloomberg School of Public Health have for the first time
identified a molecular pathway that triggers an immune response in
multiple mosquito species capable of stopping the development of
Plasmodium falciparum—the parasite that causes malaria in humans.

By silencing the gene, caspar, the researchers were able to block the development of the malaria-causing parasite in Anopheles gambiae, A. stephensi and A. albimanus mosquitoes—three mosquito species that spread malaria in Africa, Asia and the Americas.

According to the study, the transcription factor Rel 2 is a key
molecule involved in regulating several potent anti-Plasmodium defense
genes that attack the parasite in the mosquito gut. Rel 2 is activated
by the immune deficiency pathway (Imd) which, in turn, is negatively
regulated by the caspar gene; when caspar is silenced the Rel 2 is
activated. The researchers found that silencing of the caspar gene
through the manipulation of gene expression resulted in mosquitoes that
successfully blocked the development of Plasmodium falciparum
in the gut tissue. Silencing the gene known as cactus, which is part of
another pathway called Toll, was shown to have similar effect in
controlling the development of Plasmodium berghei, which causes malaria in rodents.

“When a mosquito is feeding on malaria-infected blood, the parasite
will be recognized by the mosquito’s immune system through receptors
that then start the immune response. In the wild, this response is
believed to occur too late to mount an efficient immune defense that
would kill all parasites. At least a few Plasmodia will successfully
develop inside the mosquito and enable transmission of malaria,”
explained George Dimopoulos, PhD, senior author of the study and
associate professor at the Johns Hopkins Malaria Research Institute.
“In the lab we activated this immune response in advance of infection,
giving the mosquito a head start in defeating the invading parasite.”

Dimopoulos and his colleagues Lindsey Graver and Yuemei Dong also
found that Rel 2 activation did not affect the survival and egg laying
fitness of the modified mosquitoes.

“This came as a pleasant surprise since it essentially means that we
one day could spread this trait in natural mosquito populations using
genetic modification. Furthermore, by activating Rel 2, the genetically
modified mosquitoes will attack the malaria parasite with several
independent immune factors, and this will make it very difficult for
Plasmodium to develop resistance,” said Dimopoulos.

Malaria kills over one million people worldwide each year.

Funding was provided by National Institutes of Health, the National
Science Foundation and the Johns Hopkins Malaria Research Institute.